Rivaroxaban recommended for approval for pulmonary embolism in Europe


The European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of the oral anticoagulant rivaroxaban for the treatment of pulmonary embolism and prevention of recurrent pulmonary embolism and deep vein thrombosis.

The CHMP recommendation for the approval of rivaroxaban (Xarelto, Bayer HealthCare) was issued on 18 October 2012. The decision of the European Commission on the approval is expected before the end of the year.

The recommendation to approve rivaroxaban for pulmonary embolism and deep vein thrombosis is based on the clinical findings from the pivotal, global, phase III EINSTEIN-PE study. With 4,833 patients enrolled, EINSTEIN-PE was the largest study ever conducted in the acute treatment of pulmonary embolism. The study compared the oral single-drug solution of rivaroxaban 15mg twice daily for three weeks followed by 20mg once daily with the current dual drug approach of subcutaneous enoxaparin followed by a vitamin K antagonist.

Patients in EINSTEIN-PE were treated for three, six or 12 months. Rivaroxaban demonstrated efficacy comparable to that of the current standard therapy in reducing the primary endpoint of recurrent symptomatic venous thromboembolism, a composite of symptomatic deep vein thrombosis and non-fatal or fatal pulmonary embolism, without the need for laboratory monitoring. There were 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%), p=0.003.

The principal safety endpoint of overall bleeding rates was similar between the treatment groups (10.3% with rivaroxaban and 11.4% with standard therapy, p=0.23), but rivaroxaban was associated with significantly lower rates of major bleeding (1.1% vs. 2.2%, p=0.003). Rates of other adverse events were similar in the two groups. The results from this study were published in the New England Journal of Medicine in April this year. The EINSTEIN-PE investigators concluded, “A fixed-dose regimen of rivaroxaban alone was non-inferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile”.

EINSTEIN-PE is one of three phase III studies in the global EINSTEIN programme that evaluated the safety and efficacy of rivaroxaban in the treatment of venous thromboembolism in almost 10,000 patients. The other two trials – EINSTEIN-DVT and EINSTEIN-EXT – were published together in the New England Journal of Medicine in December 2010. In December 2011, rivaroxaban received European Commission approval for the treatment of deep vein thrombosis and the prevention of recurrent deep vein thrombosis and pulmonary embolism following an acute deep vein thrombosis in adults.

To date, rivaroxaban has been approved for use in the following indications across the venous arterial thromboembolic space:

  • The prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors in more than 70 countries worldwide
  • The treatment of deep vein thrombosis and prevention of recurrent DVT and pulmonary embolism in adults in more than 70 countries worldwide
  • The prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery in more than 120 countries worldwide

Rivaroxaban was discovered by Bayer HealthCare, and is being jointly developed with Janssen Research & Development. Xarelto is marketed outside the US by Bayer HealthCare and in the US by Janssen Pharmaceuticals.